Effectiveness of Mid-Regional Pro-Adrenomedullin (MR-proADM) as Prognostic Marker in COVID-19 Critically Ill Patients: an Observational Prospective Study

Abstract Background Due to the lack of validated biomarkers to predict disease progression and mortality in COVID-19 ICU-patients, we tested the effectiveness of mid-regional pro-adrenomedullin (MR-proADM) in comparison to C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH) in predicting outcome.Methods All consecutive COVID-19 adult patients admitted between March and June 2020 to the ICU of the ‘Città della Salute e della Scienza’ hospital in Turin (Italy) were enrolled. MR-proADM, clinical and routine laboratory test were measured within 48 hours from ICU admission, on day 3, 7 and 14. Survival curves difference with MR-proADM cut-off set to 1.8 nmol/L were tested using log-rank test. Predictive ability was compared using area under the curve and 95% confidence interval of different receiver-operating characteristics curves. Potential confounding effects were tested using a logistic regression model. Results Fifty-seven patients were enrolled. ICU and overall mortality were 54.4%. Within the first 24 hours, lymphocytopenia was present in 86%; increased D-dimer and CRP levels were found in 84.2% and 87.7% respectively, while PCT values higher than 0.5 μg/L were observed in 47.4%. MR-proADM, CRP and LDH were significantly different between surviving and non-surviving patients and over time, while PCT, D-dimer and NT-pro-BNP did not show any difference between the groups and over time; lymphocytes count was different between surviving and non-surviving patients only.MR-proADM was higher in dying patients (2.65+2.33vs1.18+0.47, p=0.0001) and a higher mortality characterized patients with MR-proADM exceeding 1.8 nmol/L (p=0.0157). The logistic regression model adjusted for age, gender, cardiovascular disease, diabetes mellitus and PCT values confirmed an odds ratio equal to 10.274 (95%CI 1.970-53.578) (p=0.0057) for MR-proADM higher than 1.8 nmol/L and equal to 22.206 (95%CI 1.56-316.960) (p=0.0223) for cardiovascular disease. Overall, MR-proADM was found to have the best predictive ability (AUC=0.846 – 95%CI 0.779-0.899).Conclusions In COVID-19 ICU-patients, MR-proADM seems able to provide a more precise stratification of disease severity and mortality risk than other biomarkers. Repeated MR-proADM measurement may support a rapid and effective decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM observed in COVID-19 patients.